The long term goal of this project is to better understand the biological properties of corneal epithelial stem cells. The focus of this grant is to test the hypothesis that the limbal epithelium has a greater proliferative potential than the corneal epithelium. If this is the case, it would provide strong experimental evidence that corneal epithelial stem cells reside primarily in the limbus and may migrate toward the center of the cornea. During this granting period we will use a combination of light and transmission electron microscopy and tissue section autoradiography to study this problem using SENCAR mice, rabbits and monkeys as experimental animals. We will: 1. study the role of limbal epithelial cells during corneal wound healing; 2. study the role of limbal epithelial cells in tumorigenesis; 3. study the replacement of limbal and corneal epithelial cells by conjunctiva-derived epithelial cells; 4. study the "label-retaining cells" in corneal and limbal epithelia, and study the movement of such tagged cells. Information from these studies should allow us to decide whether limbal epithelium has a greater proliferative potential than corneal epithelium. It should also lead to a better understanding of the possible roles of the limbal and corneal epithelia in growth control, differentiation and carcinogenesis. This will ultimately increase our knowledge on the structure and function of corneal and limbal epithelia in man.